Particle separation and sorting are functions necessary in many biological and chemical processes for both macro-scale and miniaturized lab-on-chip applications. Some of the methods employed today are mechanical sieving and sedimentation—which are usually reserved for separation of large particles. Large scale water purification and mining/mineral recovery applications require large volume, high throughput, and rapid processing capabilities. Current water purification methods require sand beds and even membrane filters depending on the desired water quality. For example, mineral processing uses a spiral concentrator design where a helical trough allows heavy minerals to sediment near the center while centrifugal force pushes lighter particles outward where they are transported away. The tray has a sloped cross-section which is deeper near the axis of the helix.
Techniques such as hydrodynamic chromatography, size exclusion chromatography and electrophoresis allow separation of smaller particles. Most of these techniques have seen exponential growth but are batch processes that require set-up time for each sample lot. Field Flow Fractionation (FFF) is another macro-scale separation technique which is 30 years old but has attracted recent interest in microfluidics. This technique requires a transverse field which may be polarization, acoustic, magnetic, thermal, optical, or centrifugal, to sort and collect particles by elution. Particles are sorted by setting them at elevations that result in different flow velocity in the parabolic flow profile. Though the FFF technique is versatile and has the potential to be miniaturized, the requirement of an external field may increase the complexity of the device. Also, the use of a particular field method might limit its area of application to certain reagents (e.g. Magnetic FFF).
More recent developments in microfluidics based particle separation system include work reported by Yang et. al. (Yang S., Zhan J., Particle Separation in Microfluidic channels using flow control, Proceedings of IMECE04') based on the Zweifach-Fung effect, which involves passing the fluid through a channel bifurcation and maintaining different flow rates in each downstream daughter channel. Here the particles get moved into the daughter channel with the higher flow rate. Another approach is Pinched Flow Fractionation (PFF) (Takagi J., Yamada M., Yasuda M., Seki M., Continuous particle separation in a microchannel having asymmetrically arranged multiple branches, Lab on a chip 2005). In this method, the media and sample fluids are passed through a pinched section of a channel where the particles get aligned along the wall depending on their size and are subsequently separated downstream in the expansion region. Asymmetric Pinched Flow Fractionation (AsPFF) has also been carried out where the outlet channels have varying flow rates. This increases the resolution of the device. Continuous separation by the use of an asymmetric microfluidics cavity with a variable channel width along with modifying both flow rate and position of inlet of media and sample have been achieved by Zhang et. al. (Zhang X., Cooper J., Monaghan P., Haswell S., Continuous flow separation of particle within an asymmetric microfluidic device, Lab on a chip 2006). The phenomenon is based widely on ‘pinched inlet’ effect where the sample fluid and media fluid is passed side-by-side through a narrow section of the channel. Thus, the different sized particles are placed in different positions along the channel depending on their diameter. This section expands gradually and asymmetrically along the length and the particles, on the virtue of their initial position in the narrow section, get placed differentially downstream where the flow profile diverges and the separation thus amplifies owing to the laminar parabolic velocity profile. SPLITT Fractionation is another method used to separate and sort particles (Narayanan N., Saldanha A., Gale B., A microfabricated electrical SPLITT system, Lab on a chip 2005), which essentially utilize compression of the sample flow stream by media flow stream right at the inlet. The separation is achieved downstream. Ultrasonic particle separation is another way in which particles get arranged along a pressure node in the fluidic channel on the application of an acoustic field across the channel width (Kapishnikov S., Kantsler V., Steinberg V., Continuous particle size separation and size sorting using ultrasound in a microchannel, J. Stat. Mech. (2006) P01012). The particles can be collected downstream and separated from the flow by carefully modifying the downstream geometry. Size based separation may also be possible with this method by use of serpentine channels with the extractions ports as specific intervals. Microfluidics based centrifugal separation has been reported by Brenner (Brenner T., Polymer Fabrication and Microfluidic Unit Operations for Medical Diagnostics on a Rotating Disk, Dissertation at Institute of Microsystems, University of Frieburg, December 2005). This essentially is a miniature centrifuge constructed on a rotating disk with polymer microstructures to carry the fluid. Finally, Ookawara (Ookawara, S., Higashi, R., Street, D., and Ogawa, K. Feasibility Study on Concentrator of Slurry and Classification of Contained Particles by Micro-Channel, Chem. Eng. J., v. 101, 171-178 (2004)) reported on the use of 200 μm×170 μm microchannels with semicircular radius of 2 mm for centrifugal separation where slurry particles are directed into one arm of a bifurcation channel. The rectangular (170 μm×200 μm) cross-section leads to Dean's vortices in the transverse plane which enhance mixing and re-dispersion.
Difficulties with these types of implementations have been experienced, however. For example, all of these approaches require an additional external force, are limited to batch processing and are scaled only to handle small volumes of a sample.
Another important application of particle separation is bio defense—where the challenge is to determine and detect biological threats in the water supply. The DoD has set standards for expected limit of detection (LOD) for a list of potential agents. In particular, the Tri-Service Standard for anthrax spores is 100 cfus/L, which poses a significant challenge in logistics, time, and concentration factor. Neglecting all losses, at least 1000 L of water must be screened with a concentration factor of 106 for a typical detector sensitivity of 105 cfus/mL. The most popular method for screening large volumes of water is tangential flow filtration (TFF) with low molecular weight cut-off (MWCO) membranes (typically 30 KDa). The biggest challenge to this method and to all these vendors is the low yield and laborious back-flush recovery of captured pathogens from these membranes.